This project, A Longitudinal Study of the Durability of Valganciclovir Therapy on Long-Term Hearing and Neurodevelopmental Outcomes in Adolescents Treated During Infancy for Symptomatic Congenital Cytomegalovirus (CMV) Diseases, will be led by David W. Kimberlin, MD. It uses a randomized cohort from an earlier study of the treatment of infants with symptomatic congenital CMV disease to ascertain whether the treatment benefits on hearing and developmental outcomes seen to 2 years of age persist over the ensuing decade. That study, known as the CASG 112 trial, was conducted by the Collaborative Antiviral Study Group and enrolled 109 subjects between 2008 and 2011. It documented that a 6 month duration of treatment of symptomatic congenital CMV provided superior hearing and developmental outcomes compared with 6 weeks of antiviral treatment, and that these benefits persisted to 2 years of age. What is not known, though, is whether these benefits persist longer than this, and whether there are any longer-term toxicities from valganciclovir therapy provided very early in life. Subjects previously enrolled in the CASG 112 study are approaching their 12th birthday. We will bring them back when they are 12 years of age for hearing and developmental assessments. Returning subjects also will have a pubertal assessment as a marker for potential gonadotoxicity from the earlier valganciclovir therapy, and for inquiry about development of any cancers. The results of this study will be important. If these benefits on hearing and development are durable, it suggests that treatment does not need to be longer than 6 months duration. On the other hand, if the benefits of 6 months of treatment are not durable (that is, if they wane over time), this is of equal value because it illumines the next study that needs to be conducted to assesses treatment of perhaps 12 months (or even longer), with or without the addition of a second antiviral drug such as letermovir. Also, if longer-term toxicities from the earlier valganciclovir therapy are identified, this will have a direct impact on the clinical treatment of patients with symptomatic congenital CMV disease. Most importantly, knowledge will be gained from this longitudinal study of long-term hearing and developmental outcomes following what is now the standard duration of treatment (6 months) that will benefit children who have received this course of therapy.